{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:42:35Z","timestamp":1784893355084,"version":"3.55.0"},"reference-count":62,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lundbeck Foundation Research Initiative on Brain Barriers and Drug Delivery","award":["R155-2013-14113"],"award-info":[{"award-number":["R155-2013-14113"]}]},{"name":"Lundbeck Foundation Research Initiative on Brain Barriers and Drug Delivery","award":["A38230"],"award-info":[{"award-number":["A38230"]}]},{"name":"Danish Multiple Sclerosis Society","award":["R155-2013-14113"],"award-info":[{"award-number":["R155-2013-14113"]}]},{"name":"Danish Multiple Sclerosis Society","award":["A38230"],"award-info":[{"award-number":["A38230"]}]},{"name":"Parkinsonforeningen","award":["R155-2013-14113"],"award-info":[{"award-number":["R155-2013-14113"]}]},{"name":"Parkinsonforeningen","award":["A38230"],"award-info":[{"award-number":["A38230"]}]},{"name":"Svend Andersen Fonden","award":["R155-2013-14113"],"award-info":[{"award-number":["R155-2013-14113"]}]},{"name":"Svend Andersen Fonden","award":["A38230"],"award-info":[{"award-number":["A38230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood\u2013brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries using the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods: Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results: In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA, returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females, receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. The uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA despite upregulated TfR expression. Conclusions: VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.<\/jats:p>","DOI":"10.3390\/cells13141181","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T11:30:55Z","timestamp":1720697455000},"page":"1181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Upregulation of Transferrin Receptor 1 (TfR1) but Not Glucose Transporter 1 (GLUT1) or CD98hc at the Blood\u2013Brain Barrier in Response to Valproic Acid"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2452-7504","authenticated-orcid":false,"given":"Steinunn Sara","family":"Helgud\u00f3ttir","sequence":"first","affiliation":[{"name":"Neurobiology Research and Drug Delivery (NRD), Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper Bendix","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Section for Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark, 2800 Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3658-5859","authenticated-orcid":false,"given":"Lisa Greve","family":"Routhe","sequence":"additional","affiliation":[{"name":"Neurobiology Research and Drug Delivery (NRD), Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte Laurfelt Munch","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Neurobiology Research and Drug Delivery (NRD), Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-7039","authenticated-orcid":false,"given":"Maj Schneider","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Neurobiology Research and Drug Delivery (NRD), Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-0207","authenticated-orcid":false,"given":"Torben","family":"Moos","sequence":"additional","affiliation":[{"name":"Neurobiology Research and Drug Delivery (NRD), Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s10545-013-9608-0","article-title":"Blood-Brain Barrier Structure and Function and the Challenges for CNS Drug Delivery","volume":"36","author":"Abbott","year":"2013","journal-title":"J. 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